3-179198731-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006218.4(PIK3CA):c.-76-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0124 in 634,656 control chromosomes in the GnomAD database, including 298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0088 (42 hom., cov: 32)
  • Exomes 𝑓: 0.014 (256 hom.)
• Consequence: PIK3CA NM_006218.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.27

Genes affected

PIK3CA (HGNC:8975): (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) Phosphatidylinositol 3-kinase is composed of an 85 kDa regulatory subunit and a 110 kDa catalytic subunit. The protein encoded by this gene represents the catalytic subunit, which uses ATP to phosphorylate PtdIns, PtdIns4P and PtdIns(4,5)P2. This gene has been found to be oncogenic and has been implicated in cervical cancers. A pseudogene of this gene has been defined on chromosome 22. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 3-179198731-T-C is Benign according to our data. Variant chr3-179198731-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1181592.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr3-179198731-T-C is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PIK3CA	NM_006218.4	c.-76-19T>C		intron_variant		ENST00000263967.4
PIK3CA	XM_006713658.5	c.-76-19T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PIK3CA	ENST00000263967.4	c.-76-19T>C		intron_variant		2	NM_006218.4	P1

Frequencies

GnomAD3 genomes AF: 0.00882 AC: 1343 AN: 152198 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.00868

Gnomad FIN AF: 0.00198

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00738

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.0136 AC: 6555 AN: 482340 Hom.: 256 Cov.: 6 AF XY: 0.0133 AC XY: 3320 AN XY: 249972

Gnomad4 AFR exome AF: 0.00147

Gnomad4 AMR exome AF: 0.00287

Gnomad4 ASJ exome AF: 0.00214

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.00524

Gnomad4 FIN exome AF: 0.00253

Gnomad4 NFE exome AF: 0.00746

Gnomad4 OTH exome AF: 0.00954

GnomAD4 genome AF: 0.00879 AC: 1339 AN: 152316 Hom.: 42 Cov.: 32 AF XY: 0.00934 AC XY: 696 AN XY: 74490

Gnomad4 AFR AF: 0.00180

Gnomad4 AMR AF: 0.00484

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.117

Gnomad4 SAS AF: 0.00869

Gnomad4 FIN AF: 0.00198

Gnomad4 NFE AF: 0.00738

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00860 Hom.: 3

Bravo AF: 0.00954

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	10
Dann	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11709323; hg19: chr3-178916519; COSMIC: COSV55877393;